Complication rates following operative treatment of calcaneus fractures.

BACKGROUND: The purpose of this study is to report the short-term complication rates and mid-term subtalar fusion rates following operative management of calcaneal fractures. METHODS: This is a retrospective study of Californians undergoing operative treatment of a calaneus fracture from 1995 to 2005. The main outcomes reported are readmission for a short-term complication within 90 days of surgery and reoperation for subtalar fusion during the observation period. RESULTS: We identified 4481 patients who underwent open reduction and internal fixation of their fracture as inpatients within 30 days of the index admission. The short-term rate of complications included a 90-day rate of readmission of 1.03% for wound infection, 0.25% for thromboembolic disease, and 0.22% for mortality. The mid-term rate of subtalar fusion was 3.49% at 5 years post-operatively. CONCLUSIONS: This study reports the short-term complication rates and mid-term subtalar fusion rates following operative management of calcaneal fractures using population-based data.

Incidence and factors predicting pulmonary embolism and deep venous thrombosis following surgical treatment of ankle fractures.

BACKGROUND: The purpose of this study was to identify the incidence and risk factors associated with pulmonary embolism and deep venous thrombosis following open reduction and internal fixation of ankle fractures. METHODS: This was a retrospective study of patients in California undergoing operative treatment of an ankle fracture from 1995 to 2005. The main outcome measure was readmission for pulmonary embolism or deep venous thrombosis within 90 days of surgery. RESULTS: A total of 57,183 patients from the California discharge database were identified. The readmission rate for pulmonary embolism was low at 0.34%. The risk was increased in patients aged 50-75, those with open fractures, and those with higher Charlson comorbidity score. The overall rate of readmission for deep venous thrombosis was also low at 0.05%. CONCLUSIONS: The overall rate of thromboembolic disease was low in this large patient sample. Increased age and comorbidity were associated with an increased risk.

Variations in the quality of care delivered to patients undergoing total knee replacement at 3 affiliated hospitals.

While excellent clinical results have been seen with total knee replacement (TKR), extensive documentation exists in variations in outcomes due to factors such as hospital and surgeon volume. The hypothesis of this study was that statistically significant variation exists in the processes of care delivered to patients undergoing TKR at 3 affiliated hospitals.Retrospective chart review was used to compare the quality of care delivered to a sample of patients from an academic medical center, public county hospital, and private community hospital. Two hundred twenty-four patients undergoing primary TKR were included. Quality of care was measured by determining adherence to a set of 31 evidence-based quality indicators created using the RAND/UCLA modified Delphi expert panel methodology. The overall rate of adherence to the quality indicators was 53% (95% confidence interval [CI], 52%-55%) for the 224 patients. There was a statistically significant difference between sites, with patients treated at the high-volume academic center demonstrating a 58% rate of adherence (95% CI, 56%-61%) compared with 50% (95% CI, 48-51%; P =.008) at the lower-volume public hospital and 52% (95% CI, 51%-54%; P =.03) at the lower-volume private hospital.Further study is warranted to determine the extent of variation in the delivery of care and its relationship to variation in outcomes of care for patients undergoing TKR.

Factors predicting complication rates after primary shoulder arthroplasty.

HYPOTHESIS: Shoulder arthroplasty is an effective treatment for arthritic conditions and intraarticular fractures of the proximal humerus. Treatment options include total and hemiarthroplasty of the shoulder. They hypothesis of this study was that a mandatory statewide discharge database could identify the epidemiology of primary shoulder arthroplasty, 90 day complication rates, implant survival rates, and patient and hospital characteristics associated with complications. MATERIALS AND METHODS: We identified patients undergoing primary total shoulder replacement and hemiarthroplasty between 1995 and 2005. We report rates of complications within 90 days of surgery and performed survival analysis using revision surgery as the endpoint. Logistic and proportional hazard regression models were used to estimate the effect of patient and provider factors in predicting the rates of adverse outcomes. RESULTS: During the study period, 15,288 patients underwent shoulder arthroplasty. Patients undergoing total shoulder arthroplasty and hemiarthroplasty had no statistically significant difference in the aggregate risk of 90-day complications or the risk of implant failure within the study period. Fracture patients were shown to have a higher risk of short-term complications (odds ratio, 3.2; P < .001). Implant failure rates were lower in patients with fracture, rheumatoid arthritis, increased comorbidity, and advanced age. CONCLUSION: This study reports similar rates of short-term complications and implant failure in patients undergoing total or hemiarthroplasty, an overall mortality rate of 1.3%, and a pulmonary embolism rate of 0.6%. The findings of our study indicate that the risk of short-term complications is highest in patients undergoing total or hemiarthroplasty for a fracture compared with nonfracture indications. Our results also indicate that longer-term, implant survival is largely driven by factors associated with increased activity, such as age. In patients undergoing surgery for arthritis of the shoulder, we found no difference in implant survival rates between total and hemiarthroplasty of the shoulder.

Complication and revision rates following total elbow arthroplasty.

PURPOSE: To determine the complication rates after total elbow arthroplasty (TEA) in a large and diverse patient population. METHODS: We identified patients undergoing TEA as inpatients in the years 1995 to 2005 using California's Discharge Database. Short-term outcomes of interest included rates of infection or wound complications, revision, reoperation, and pulmonary embolism that were diagnosed during an inpatient hospital admission and mortality within 90 days of index surgery. Longer-term outcomes analyzed included rates of revision, amputation, and conversion to fusion. We used regression models to estimate the role of patient and provider characteristics in predicting the rates of adverse outcomes. RESULTS: We identified 1,625 patients undergoing TEA. Early complications, defined as those requiring inpatient re-admission within the first 90 days after index surgery, were identified in 170 patients, and 132 patients required reoperation. Eighty one patients required revision in 90 days, and 48 underwent revision within one year. Early infections and wound complications requiring readmission occurred in 88 patients. In the 90 days after surgery, 4 patients had a pulmonary embolism and 10 patients died. One-hundred and twenty-one patients required revision, amputation, or fusion during the observation period, with a mean follow-up of 4 years. Hospital volume was not associated with increased risk of adverse outcomes. CONCLUSIONS: We analyzed a large and diverse patient population undergoing TEA. The overall rate of short-term complications requiring inpatient treatment was high, at over 10% (170 patients), with almost 8% (132 patients) requiring reoperation within the first 90 days. Although population-based studies have shortcomings, they can add to the body of knowledge of less frequent procedures such as TEA. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Complication rates following open reduction and internal fixation of ankle fractures.

BACKGROUND: Ankle fractures are among the most common injuries treated by orthopaedic surgeons. The purpose of the present investigation was to examine the risks of complications after open reduction and internal fixation of ankle fractures in a large population-based study. METHODS: With use of California's discharge database, we identified 57,183 patients who had undergone open reduction and internal fixation of a lateral malleolar, bimalleolar, or trimalleolar ankle fracture as inpatients in the years 1995 through 2005. Short-term complications were examined on the basis of the rates of readmission within ninety days after discharge. The intermediate-term rate of reoperation for ankle fusion or arthroplasty was also analyzed. Logistic regression and proportional hazard regression models were used to determine the strength of the relationships between the rates of complications and fracture type, patient demographics and comorbidities, and hospital characteristics. RESULTS: The overall rate of short-term complications was low, including the rates of pulmonary embolism (0.34%), mortality (1.07%), wound infection (1.44%), amputation (0.16%), and revision open reduction and internal fixation (0.82%). The intermediate-term rates of reoperation were also low, with ankle fusion or ankle replacement being performed in 0.96% of the patients who were observed for five years. Open fractures, age, and medical comorbidities were significant predictors of short-term complications. The presence of complicated diabetes was a particularly strong predictor (odds ratio, 2.30; p < 0.001), as was peripheral vascular disease (odds ratio, 1.65; p < 0.001). The intermediate-term rate of reoperation for ankle fusion or replacement was higher in patients with trimalleolar fractures (hazard ratio, 2.07; p < 0.001) and open fractures (hazard ratio, 5.29; p < 0.001). Treatment at a low-volume hospital was not significantly associated with either the aggregate risk of short-term complications or the risk of intermediate-term reoperation. CONCLUSIONS: By analyzing a large, diverse patient population, the present study clarifies the risks associated with open reduction and internal fixation of ankle fractures. Open injury, diabetes, and peripheral vascular disease were strong risk factors predicting a complicated short-term postoperative course. Fracture type was a strong predictor of reoperation for ankle fusion or replacement. Hospital volume did not play a significant role in the rates of short-term or intermediate-term complications.

Stem cells from human fat as cellular delivery vehicles in an athymic rat posterolateral spine fusion model.

BACKGROUND: Mesenchymal stem cells derived from human liposuction aspirates, termed processed lipoaspirate cells, have been utilized as cellular delivery vehicles for the induction of bone formation in tissue engineering and gene therapy strategies. In this study, we sought to evaluate the efficacy of bone morphogenetic protein (BMP)-2-producing adipose-derived stem cells in inducing a posterolateral spine fusion in an athymic rat model. METHODS: Single-level (L4-L5) intertransverse spinal arthrodesis was attempted with use of a type-I collagen matrix in five groups of athymic rats, with eight animals in each group. Group I was treated with 5 x 10(6) adipose-derived stem cells transduced with an adenoviral vector containing the BMP-2 gene; group II, with 5 x 10(6) adipose-derived stem cells treated with osteogenic media and 1 microg/mL of recombinant BMP-2 (rhBMP-2); group III, with 10 microg of rhBMP-2; group IV, with 1 microg of rhBMP-2; and group V, with 5 x 10(6) adipose-derived stem cells alone. The animals that showed radiographic evidence of healing were killed four weeks after cell implantation and were examined with plain radiographs, manual palpation, microcomputed tomography scanning, and histological analysis. RESULTS: All eight animals in group I demonstrated successful spinal fusion, with a large fusion mass, four weeks postoperatively. Furthermore, group-I specimens consistently revealed spinal fusion at the cephalad level (L3 and L4), where no fusion bed had been prepared surgically. In contrast, despite substantial BMP-2 production measured in vitro, group-II animals demonstrated minimal bone formation even eight weeks after implantation. Of the groups treated with the application of rhBMP-2 alone, the one that received a relatively high dose (group III) had a higher rate of fusion (seen in all eight specimens) than the one that received the low dose (group IV, in which fusion was seen in four of the eight specimens). None of the group-V animals (treated with adipose-derived stem cells alone) demonstrated successful spine fusion eight weeks after the surgery. CONCLUSIONS: Adipose-derived stem cells show promise as gene transduction targets for inducing bone formation to enhance spinal fusion in biologically stringent environments.

Mixed metastatic lung cancer lesions in bone are inhibited by noggin overexpression and Rank:Fc administration.

UNLABELLED: Lung cancer metastases to bone produce a primarily mixed osteolytic/osteoblastic lesion. The purpose of this study was to determine if blockade of both pathways would inhibit the formation these lesions in bone. Inhibition of the osteoblastic lesion with noggin and the osteolytic lesion with RANK:Fc was a successful treatment strategy to inhibit progression of mixed lung cancer lesions in bone. INTRODUCTION: Approximately 9-30% of patients with lung cancer develop bone metastases, leading to significant morbidity and mortality. A549 is a non-small-cell lung cancer (NSCLC) line that produces a mixed metastatic lesion in bone. We sought to determine if blockade of key components in both osteolytic and osteoblastic pathways would result in a reduction of a NSCLC tumor progression in a murine model of bony metastasis. MATERIALS AND METHODS: The study used a retroviral vector overexpressing noggin (RN), a specific inhibitor of BMP, and RANK:Fc, a chimeric protein that inhibits the RANK-RANKL interaction. A549 cells were transduced with RN before implantation in SCID mice. Cells were implanted in a subcutaneous model and tibial injection model. RANK:Fc was administered twice weekly at 15 mg/kg. There were five treatment groups: A549; A549 + RN; A549 + RANK:Fc; A549 + empty vector; and A549 + RN + RANK:Fc (n = 10/group). RESULTS: In SCID mice who underwent subcutaneous A549 tumor cell injection, animals treated with A549 + RN had significantly smaller subcutaneous tumor size at 8 weeks. In an intratibial model of bony metastasis, animals injected with A549 cells developed a mixed lytic/blastic lesion with cortical destruction at 8 weeks. Treatment with RANK:Fc inhibited the formation of osteoclasts, led to a smaller tumor volume in bone, and inhibited the lytic component of the mixed lesion. Animals treated with A549 + RN had a decreased number of osteoblasts in bone lesions, smaller tumor volume, and inhibition of the blastic component of the mixed lesions. Combination treatment inhibited both the lytic and blastic components of the lesion. CONCLUSIONS: The NSCLC cell line A549 forms a mixed osteolytic/osteoblastic lesion in vivo. Noggin overexpression inhibited the formation of the osteoblastic aspect of the lesion in bone and the tumor growth in vivo. Treatment with RANK:Fc limited the formation of the lytic aspect of the mixed lesion and also inhibited the rate of in vivo tumor growth. Inhibition of both pathways is necessary to effectively inhibit the progression of mixed metastatic lesions in bone.

In vivo molecular imaging of adenoviral versus lentiviral gene therapy in two bone formation models.

Regional gene therapy techniques are promising methods to enhance bone formation in large bone defects that would be difficult to treat with allograft or autograft bone stock. In this study, we compared in vivo temporal expression patterns of adenoviral- and lentiviral-mediated gene therapy in two bone formation models. Primary rat bone marrow cells (RBMC) were transduced with lentiviral or adenoviral vectors containing luciferase (Luc) or BMP-2 cDNA, or cotransduced with vectors containing Luc and bone morphogenetic protein 2 (BMP-2). In vitro protein production was determined with luciferase assay or ELISA (for BMP-2 production) weekly for 12 weeks. Two bone formation models were used -- a hind limb muscle pouch or radial defect -- in SCID mice. A cooled charged-coupled device (CCD) camera was used to image in vivo luciferase expression weekly for 12 weeks. In vitro, adenoviral expression of BMP-2 and luciferase was detected by ELISA or luciferase assay, respectively, for 4 weeks. Lentiviral expression of BMP-2 and luciferase was sustained in culture for 3 months. Using the CCD camera, we found that adenoviral vectors expressed luciferase expression for up to 21 days, but lentiviral vectors expressed target gene expression for 3 months in vivo in both bone formation models. There was no detectable difference in the amount of bone formed between the adenoviral and lentiviral groups. Lentiviral-mediated delivery of BMP-2 can induce long term in vitro and in vivo gene expression, which may be beneficial when developing tissue engineering strategies to heal large bone defects or defects with a compromised biologic environment.

Overexpression of noggin inhibits BMP-mediated growth of osteolytic prostate cancer lesions.

INTRODUCTION: Although a majority of metastatic prostate cancer lesions are osteoblastic in nature, some are mixed or lytic; and, osteoblastic lesions require osteolytic activity in order to progress. The role of BMPs in the formation of prostate cancer metastases to bone remains unknown. We hypothesized that BMPs influence the development and progression of osteolytic prostate cancer lesions. METHODS: RT-PCR and Western blot analysis were used to determine BMP receptor expression on the osteolytic prostate cancer cell line PC-3. Migration, invasion, and cellular proliferation assays were performed on PC-3 cells to quantify the effects of BMP-2, -4, and -7. In vivo, PC-3 cells were injected alone, with an empty retroviral vector, or with a retroviral vector overexpressing noggin, into the tibias of SCID mice. The animals were followed for 8 weeks, and histologic and radiographic analysis were performed at 2, 4, 6, and 8 weeks. RESULTS: BMP receptors are expressed on PC-3 cells, suggesting that they would be responsive to host BMP secretion. BMP-2, and to a lesser extent, BMP-4, stimulated PC-3 cell migration and invasion in a dose-dependent fashion. Noggin inhibited cellular migration and invasion of BMP-2 and -4 stimulated PC-3 cells. BMP-2 alone stimulated PC-3 cell proliferation, but BMP-4 had no effect. BMP-7 had no effect on proliferation, migration, or invasion. PC-3 cells implanted into SCID mouse tibias formed osteolytic lesions as early as 2 weeks and completely destroyed the proximal tibia by 8 weeks. Overexpression of noggin in PC-3 cells inhibited the expansion of the lesion in vivo. CONCLUSIONS: BMPs influence the formation of the osteolytic prostate cancer metastases, and treatment modalities that inhibit BMP activity may limit the progression of the lytic component of prostate cancer metastases.

Influence of BMPs on the formation of osteoblastic lesions in metastatic prostate cancer.

UNLABELLED: The purpose of this study was to evaluate the role of BMPs on the formation of metastatic prostate cancer lesions to bone. Our results show that BMPs influence the development and progression of osteoblastic lesions and suggest that therapies that inhibit BMP activity may reduce the formation and progression of osteoblastic lesions. INTRODUCTION: Prostate adenocarcinoma is the leading cause of cancer in North American men. The formation of skeletal metastases affects approximately 70% of patients with advanced disease, and a majority of these patients have osteoblastic lesions. Although BMPs have been found to be expressed in multiple oncogenic cell lines, their role in the formation of metastatic osteoblastic lesions remains uncharacterized. We hypothesized that BMPs influence the development of metastatic osteoblastic lesions associated with prostate cancer. MATERIALS AND METHODS: Western blot analysis and RT-PCR was used to determine BMP receptor expression on osteoblastic prostate cancer cell lines LAPC-4 and LAPC-9. Migration, invasion, and cellular proliferation assays were used to quantify the effects of BMP-2, -4, and -7 on LAPC-4 cells in vitro. LAPC-9 cells alone or transfected with a retrovirus overexpressing noggin were injected into the tibias of SCID mice, and the animals were followed for 8 weeks. Tumor size was determined by radiographs and direct measurement. Histology was performed at the time of death. RESULTS: We determined that BMP receptor mRNA and protein was expressed on osteoblastic prostate cancer cell lines LAPC-4 and LAPC-9. In vitro studies showed that BMP-2 and -7 stimulated cellular migration and invasion of prostate cancer cells in a dose-dependent fashion, although BMP-4 had no effect. Noggin inhibited cellular migration and invasion of BMP-2- and -7-stimulated LAPC-4 cells. LAPC-9 cells implanted into immunodeficient mouse tibias formed an osteoblastic lesion with sclerotic bone at 8 weeks. Formation of osteoblastic lesions was inhibited by overexpression of noggin by prostate cancer cells transduced with a retrovirus containing the cDNA for noggin. CONCLUSIONS: BMPs are critical in the formation of the osteoblastic lesions associated with prostate cancer metastases, and future treatment strategies that inhibit local BMP activity may reduce the formation and progression of osteoblastic lesions.